Identification of patients at increased risk of first unheralded acute myocardial infarction by electron-beam computed tomography.

BACKGROUND: There is a clear relationship between absolute calcium scores (CS) and severity of coronary artery disease. However, hard coronary events have been shown to occur across all ranges of CS. METHODS AND RESULTS: We conducted 2 analyses: in group A, 172 patients underwent electron-beam CT (EBCT) imaging within 60 days of suffering an unheralded myocardial infarction. In group B, 632 patients screened by EBCT were followed up for a mean of 32+/-7 months for the development of acute myocardial infarction or cardiac death. The mean patient age and prevalence of coronary calcification were similar in the 2 groups (53+/-8 versus 52+/-9 years and 96% each). In group B, the annualized event rate was 0.11% for subjects with CS of 0, 2.1% for CS 1 to 99, 4.1% for CS 100 to 400, and 4.8% for CS >400, and only 7% of the patients had CS >400. However, mild, moderate, and extensive absolute CSs were distributed similarly between patients with events in both groups (34%, 35%, and 27%, respectively, in group A and 44%, 30%, and 22% in group B). In contrast, the majority of events in both groups occurred in patients with CS >75th percentile (70% in each group). CONCLUSIONS: Coronary calcium is present in most patients who suffer acute coronary events. Although the event rate is greater for patients with high absolute CSs, few patients have this degree of calcification on a screening EBCT. Conversely, the majority of events occur in individuals with high CS percentiles. Hence, CS percentiles constitute a more effective screening method to stratify individuals at risk.

Severity of coronary artery calcification by electron beam computed tomography predicts silent myocardial ischemia.

BACKGROUND: Detection of subclinical coronary artery disease (CAD) before the development of life-threatening cardiac complications has great potential clinical relevance. Electron beam computed tomography (EBCT) is currently the only noninvasive test that can detect CAD in all stages of its development and thus has the potential to be an excellent screening technique for identifying asymptomatic subjects with underlying myocardial ischemia. METHODS AND RESULTS: Over 2.5 years, we prospectively studied 3895 generally asymptomatic subjects with EBCT, 411 of whom had stress myocardial perfusion tomography (SPECT) within a close (median, 17 days) time period. SPECT and exercise treadmill results were compared with the coronary artery calcium score (CACS) as assessed by EBCT. The total CACS identified a population at high risk for having myocardial ischemia by SPECT although only a minority of subjects (22%) with an abnormal EBCT had an abnormal SPECT. No subject with CACS <10 had an abnormal SPECT compared with 2.6% of those with scores from 11 to 100, 11.3% of those with scores from 101 to 399, and 46% of those with scores >/=400 (P<0.0001). CACS predicted an abnormal SPECT regardless of subject age or sex. CONCLUSIONS: CACS identifies a high-risk group of asymptomatic subjects who have clinically important silent myocardial ischemia. Our results support the role of EBCT as the initial screening tool for identifying individuals at various stages of CAD development for whom therapeutic decision making may differ considerably.

Multicenter clinical trial to evaluate the efficacy of correction for photon attenuation and scatter in SPECT myocardial perfusion imaging.

BACKGROUND: Soft tissue attenuation is a prominent cause of single-photon emission computed tomography (SPECT) imaging artifacts, which may result in reduced diagnostic accuracy of myocardial perfusion imaging. A method incorporating simultaneously acquired transmission data permits nonuniform attenuation correction and when incorporating scatter correction and resolution compensation may substantially reduce interpretive errors. METHODS AND RESULTS: A prospective multicenter trial was performed recruiting patients with angiographically documented coronary disease (n=96) and group of subjects with a low likelihood of disease (n=88). The uncorrected and attenuation/scatter corrected images were read independently, without knowledge of the patient's clinical data. The detection of >/=50% stenosis was similar using uncorrected perfusion data or with attenuation/scatter correction and resolution compensation (visual or visual plus quantitative analysis), 76% versus 75% versus 78%, respectively (P=NS). The normalcy rate, however, was significantly improved with this new methodology, using either the corrected images (86% vs 96%; P=0.011) or with the corrected data and quantitative analysis (86% vs 97%; P=0.007). The receiver operator characteristic curves were also found to be marginally but not significantly higher with attenuation/scatter correction than with tradition SPECT imaging. However, the ability to detect multivessel disease was reduced with attenuation/scatter correction. Regional differences were also noted, with reduced sensitivity but improved specificity for right coronary lesions using attenuation/scatter correction methodology. CONCLUSIONS: This multicenter trial demonstrates the initial clinical results of a new SPECT perfusion imaging modality incorporating attenuation and scatter correction in conjunction with 99mTc sestamibi perfusion imaging. Significant improvements in the normalcy rate were noted without a decline in overall sensitivity but with a reduction in detection of extensive coronary disease.

Dobutamine thallium-201 tomography for evaluating patients with suspected coronary artery disease unable to undergo exercise or vasodilator pharmacologic stress testing.

OBJECTIVES: The aim of this study was to assess the feasibility, safety and diagnostic accuracy of a high dose dobutamine infusion in conjunction with thallium-201 single-photon emission computed tomography in 144 patients (72 men and 72 women with a mean age of 65 +/- 10 years) unable to perform exercise or pharmacologic vasodilator stress testing. BACKGROUND: Dobutamine increases myocardial oxygen consumption by increasing heart rate, contractility and arterial blood pressure. In addition, it causes myocardial blood flow heterogeneity and thus may be a useful stress for noninvasive detection of coronary artery disease. METHODS: Dobutamine was administered intravenously at incremental doses of 5, 10, 20, 30 and up to 40 micrograms/kg per min at 3-min intervals. After 1 min of the maximal dose, 3 mCi of thallium-201 was injected and the infusion was continued for an additional 2 min. Thallium-201 tomography was performed 5 to 10 min after termination of the infusion and 4 h later. The images were visually assessed for the presence and vascular location of perfusion defects and the extent of thallium redistribution. Coronary angiography was performed in 84 patients, with a > 50% stenosis considered significant. RESULTS: Dobutamine significantly (p = 0.0001) increased the heart rate (from 75 +/- 14 beats/min to 120 +/- 23 beats/min), systolic blood pressure (from 136 +/- 23 mm Hg to 148 +/- 35 mm Hg) and the rate-pressure product (from 10,144 +/- 2,517 to 17,858 +/- 4,349) from baseline to peak infusion rate, respectively. Most patients (75%) experienced side effects during the infusion, but 74% tolerated a dobutamine dose of 40 micrograms/kg per min and 97% a dose of 30 micrograms/kg per min. The more common side effects were typical (26%) and atypical (5%) chest pain, palpitation (29%), flushing (14%), headache (14%) and dyspnea (14%). The overall sensitivity of dobutamine tomography was 86% in the patients who underwent coronary angiography and 84% in those with single-vessel, 82% in those with double-vessel and 100% in those with triple-vessel disease. Seventy-eight percent of vessels with severe (> or = 70%) stenoses were identified with dobutamine tomography. The specificity of dobutamine tomography was 90% for patients and 86% for individual vessels. CONCLUSIONS: A high dose dobutamine infusion in conjunction with thallium tomography appears to be a well tolerated and accurate method for diagnosing coronary artery disease in patients unable to perform exercise or vasodilator pharmacologic stress testing.

The variable extent of jeopardized myocardium in patients with single vessel coronary artery disease: quantification by thallium-201 single photon emission computed tomography.

To assess the extent of jeopardized myocardium in patients with single vessel coronary artery disease of variable severity and location, quantitative exercise thallium-201 single photon emission computed tomography was performed in 158 consecutive patients with angiographically proved single vessel coronary artery disease. The extent of abnormal left ventricular perfusion was quantified from computer-generated polar maps of three-dimensional myocardial radioactivity. Patients with only a moderate (51% to 69%) stenosis tended to have a small perfusion defect irrespective of the coronary artery involved. Whereas a perfusion defect measuring greater than or equal to 10% of the left ventricle was found in 78% of patients with no prior infarction and severe (greater than or equal to 70%) stenosis, this was observed in only 24% of patients with moderate stenosis. Perfusion defect size increased with increasing severity of stenosis for the entire group without infarction and for those with left anterior descending, right and circumflex coronary artery stenosis. However, the correlation between stenosis severity and perfusion defect size was at best only modest (r = 0.38, p = 0.0001). The left anterior descending artery was shown to be the most important of the three coronary arteries for providing left ventricular perfusion. Proximal stenosis of this artery produced a perfusion defect approximately twice as large as that found in patients with a proximal right or circumflex artery stenosis. However, marked heterogeneity in perfusion defect size existed among all three vessels despite comparable stenosis severity. This was most apparent for the left anterior descending coronary artery, where mid vessel stenosis commonly produced a perfusion defect similar in size to that found in proximally stenosed vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative thallium-201 single-photon emission computed tomography during maximal pharmacologic coronary vasodilation with adenosine for assessing coronary artery disease.

The diagnostic value of maximal pharmacologic coronary vasodilation with intravenously administered adenosine in conjunction with thallium-201 single-photon emission computed tomography (SPECT) for detection of coronary artery disease was investigated in 101 consecutive patients who had concomitant coronary arteriography. Tomographic images were assessed visually and from computer-quantified polar maps of the thallium-201 distribution. Significant coronary artery disease, defined as greater than 50% luminal diameter stenosis, was present in 70 patients. The sensitivity for detecting patients with coronary artery disease using quantitative analysis was 87% in the total group, 82% in patients without myocardial infarction and 96% in those with prior myocardial infarction; the specificity was 90%. The sensitivity for diagnosing coronary artery disease in patients without infarction with single-, double-and triple-vessel disease was 76%, 86% and 90%, respectively. All individual stenoses were identified in 68% of patients with double-vessel disease and in 65% of those with triple-vessel disease. The extent of the perfusion defects, as quantified by polar maps, was directly related to the extent of coronary artery disease. In conclusion, quantitative thallium-201 SPECT during adenosine infusion has high sensitivity and specificity for diagnosing the presence of coronary artery disease, localizing the anatomic site of coronary stenosis and identifying the majority of affected vascular regions in patients with multivessel involvement.

Equivalence between adenosine and exercise thallium-201 myocardial tomography: a multicenter, prospective, crossover trial.

OBJECTIVES: The study was designed to compare pharmacologic and exercise stress during thallium-201 single-photon tomography in a multicenter prospective crossover trial. BACKGROUND: Both exercise and adenosine myocardial perfusion imaging have high sensitivity and specificity for detection of coronary artery disease. However, few data are available comparing these two stress tests in the same patients. METHODS: The study group consisted of 175 subjects: 55 healthy volunteers and 120 patients with suspected coronary artery disease. All subjects underwent two thallium tomographic tests performed 30 days apart, one during intravenous administration of adenosine (140 micrograms/kg per min for 6 min) and one during exercise stress. All images were computer quantified and interpreted without knowledge of the stress test performed. Interpretation agreement was assessed by kappa and Z statistics. RESULTS: Agreement on the presence of normal or abnormal tomograms by adenosine and exercise scintigraphy was 82.8% by visual analysis with kappa and Z statistics of 0.65 (p less than 0.0001) and 11.1 (p less than 0.00001), respectively. The agreement by computer quantification was 86% with kappa and Z statistics of 0.709 (p less than 0.0001) and 12.2 (p less than 0.00001), respectively. Agreement on localization of the perfusion defect to a specific coronary vascular territory varied from 82.7% to 91.4% with highly significant kappa and Z statistics (p less than 0.0001). There was a good correlation between quantified perfusion defect size by adenosine and exercise (r = 0.80, p less than 0.0001), but the values for defect size were significantly greater by adenosine scintigraphy (p = 0.0073). Adenosine side effects were frequent but transient and ceased spontaneously in most subjects within 1 to 2 min after the infusion was discontinued. CONCLUSIONS: Adenosine thallium-201 scintigraphy provides diagnostic information similar to that of exercise scintigraphy, although values for defect sizes are greater with adenosine.

Adenosine thallium-201 tomography in evaluation of graft patency late after coronary artery bypass graft surgery.

OBJECTIVES: We sought to ascertain the utility of adenosine thallium-201 tomography for assessing graft stenoses late after coronary artery bypass graft surgery. BACKGROUND: Although pharmacologic perfusion imaging has been increasingly used in the assessment of patients with coronary artery disease, the value of this stress modality for detecting coronary artery bypass graft stenosis late after surgery is unknown. METHODS: We studied 109 patients who underwent both adenosine thallium-201 tomography and coronary angiography at 6.7 +/- 4.8 (mean +/- SD) years after coronary artery bypass graft surgery. Adenosine thallium-201 tomography was assessed quantitatively by computer-generated polar maps of the myocardial thallium-201 activity. RESULTS: On coronary angiography, significant graft stenoses were present in 68 patients, 65 of whom had a corresponding perfusion defect as shown by thallium-201 tomography (sensitivity 96%). Significant stenoses were present in 107 (37.8%) of 283 grafts. The overall specificity by quantitative tomography was 61%. Seventy percent of the apparently false positive perfusion defects could be explained on the basis of unbypassed native disease or by the presence of fixed defects in patients with previous myocardial infarction. CONCLUSIONS: Thus, results of adenosine thallium-201 tomography are nearly always abnormal in patients with late coronary graft stenosis. Most of the false positive defects appear to be due to either unbypassed native disease or a previous myocardial infarction.

Role of adenosine thallium-201 tomography for defining long-term risk in patients after acute myocardial infarction.

OBJECTIVES: This study prospectively evaluated whether early assessment with adenosine thallium-201 tomography could better refine risk stratification on the basis of absolute extent of myocardial ischemia in postinfarction patients in clinically stable condition. BACKGROUND: Postinfarction patients are at increased risk for subsequent cardiac events. However, identifying high risk patients among those with residual myocardial ischemia is suboptimal. METHODS: All 146 patients enrolled underwent assessment of left ventricular function and had adenosine tomography performed early (mean [+/- SD] 5 +/- 3 days) after infarction. Excluded from analysis were 51 patients with revascularization after scintigraphy and 3 lost to follow-up. Statistical risk models were therefore generated from the remaining 92 patients. RESULTS: Cardiac events occurred in 30 (33%) of 92 patients over 15.7 +/- 4.9 months. Univariate predictors of all events were quantified perfusion defect size (p < 0.0001), absolute extent of left ventricular ischemia (p < 0.000001) and ejection fraction (p < 0.0001). Risk was best predicted by Cox analysis on the basis of 1) absolute extent of ischemia and ejection fraction (chi-square 24.6); 2) percent infarct zone ischemia and ejection fraction (chi-square 24.4); or 3) total perfusion defect size and percent infarct zone ischemia (chi-square 18.9). The variables that predicted all cardiac events were equally powerful at predicting only death and nonfatal reinfarction. Death was best predicted by total perfusion defect size. CONCLUSIONS: Risk analysis of individual patients early after infarction is feasible on the basis of the quantified extent of scintigraphic ischemia and severity of left ventricular dysfunction.

Criteria for the accurate interpretation of changes in left ventricular ejection fraction and cardiac volumes as assessed by rest and exercise gated radionuclide angiography.

Although serial left ventricular ejection fraction and volumetric measurements using gated radionuclide angiography are commonly used to evaluate clinical changes and therapeutic outcomes in individual patients, criteria are not available for accurately interpreting whether a change in any of these hemodynamic measurements is clinically meaningful. Accordingly, the magnitude of inherent variability among sequential measurements of hemodynamic variables assessed by gated radionuclide angiography was investigated in a double-blind placebo-controlled fashion in 39 patients during two placebo periods separated by 6 weeks. All patients analyzed had remained clinically stable during the study period. Although the mean values for all hemodynamic variables between the two placebo periods were minimally changed, the differences in individual patients were striking. Criteria were developed to allow meaningful interpretation of changes in hemodynamic variables by estimating the likelihood that an observed change is due to variability alone. On the basis of this analysis of placebo radionuclide angiographic data, variation due to chance alone is unlikely to account for all variability if a change observed between the two rest gated studies in a patient is greater than or equal to 7% units for left ventricular ejection fraction, greater than or equal to 45 ml/m2 for end-diastolic volume index, greater than or equal to 35 ml/m2 for end-systolic volume index, greater than or equal to 20 ml/m2 for stroke volume index and greater than or equal to 1.25 liters/min per m2 for cardiac index. An observed 4% unit change in left ventricular ejection fraction (increase or decrease) after a medical intervention in an individual patient occurs by random variation greater than 25% of the time.(ABSTRACT TRUNCATED AT 250 WORDS)

Tolerance and safety of pharmacologic coronary vasodilation with adenosine in association with thallium-201 scintigraphy in patients with suspected coronary artery disease.

Adenosine thallium-201 myocardial scintigraphy is a promising test for coronary artery disease detection, but its safety has not been reported in large patient cohorts. Accordingly, the tolerance and safety profile of adenosine infusion were analyzed in 607 patients (351 men, 256 women, mean age 63 +/- 11 years) undergoing this test either because of suspected coronary artery disease (Group I, n = 482) or for risk stratification early (5.2 +/- 2.8 days) after myocardial infarction (Group II, n = 125). Adenosine increased the heart rate from 74.5 +/- 14.0 to 91.8 +/- 15.9 beats/min (p less than 0.001) and decreased systolic blood pressure from 137.8 +/- 26.8 to 120.7 +/- 26.1 mm Hg (p less than 0.001). Side effects were frequent and similar in both groups. Flushing occurred in 35%, chest pain in 34%, headache in 21% and dyspnea in 19% of patients. Only 35.6% of Group I patients with chest pain during adenosine infusion had concomitant transient perfusion abnormalities, compared with 60.7% of Group II patients (p less than 0.05). First- and second-degree AV block occurred in 9.6% and 3.6% of patients, respectively, and ischemic ST changes in 12.5% of cases. Concomitance of chest pain and ischemic ST depression was uncommon (6%) but, when present, predicted perfusion abnormalities in 73% of patients. Most side effects ceased rapidly after stopping the adenosine infusion. The side effects were severe in only 1.6% of patients and in only six patients (1%) was it necessary to discontinue the infusion. No serious adverse reactions such as acute myocardial infarction or death occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative thallium-201 single photon emission computed tomography after oral dipyridamole for assessing the presence, anatomic location and severity of coronary artery disease.

The objective of this investigation was to determine whether analysis of thallium-201 images as detected by quantitative single photon emission computed tomography after a single high oral dose of dipyridamole (300 mg) would accurately detect the presence of coronary artery disease and the anatomic location of the individual stenosis. Analyses were performed on 100 patients who concomitantly underwent diagnostic coronary arteriography and myocardial imaging. Tomographic myocardial perfusion defects were quantified using computer-generated polar maps. Eighty-four patients had significant coronary artery disease defined as greater than 50% luminal diameter stenosis. The sensitivity for detecting patients with coronary disease was 92% overall, 89% in patients without previous myocardial infarction and 97% in those with prior infarction. The technique had a sensitivity of 80, 87 and 51% for localizing coronary artery stenosis of the left anterior descending, the right coronary and the left circumflex artery, respectively. The corresponding specificity was 84, 92 and 92%. Furthermore, the presence of severe (greater than or equal to 70%) multivessel disease was identified with a sensitivity of 79% and a specificity of 87%. In conclusion, quantitative thallium-201 single photon emission computed tomography after oral dipyridamole has high sensitivity and specificity for diagnosing the presence of coronary disease, ascertaining the location of stenosed vessels and identifying the presence of multivessel disease.

Association of angiotensin I-converting enzyme gene polymorphism with myocardial ischemia and patency of infarct-related artery in patients with acute myocardial infarction.

OBJECTIVES: We determined the influence of angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism on the extent of myocardial ischemia in patients with acute myocardial infarction. BACKGROUND: The I/D polymorphism, which in part controls plasma and tissue expression of ACE, has been implicated in predisposition to myocardial infarction and ventricular remodeling. METHODS: I/D genotyping, predischarge adenosine-thallium-201 perfusion tomography and radionuclide angiography were performed in 113 patients (72 men, 41 women) with a diagnosis of acute myocardial infarction. A subgroup of 96 patients also underwent coronary angiography. RESULTS: Genotypes DD, ID and II were present in 27, 56 and 30 patients, respectively. There was no significant difference in the baseline characteristics of patients, total creatine kinase, peak MB fraction, Killip class, mean ejection fraction or the number of diseased vessels in patients with the DD, ID or II genotype. However, the size of the total and the reversible perfusion defects was greater in those with DD than in those with ID or II genotype (total defect size [mean +/- SD] 33.7 +/- 22.5%, 29.5 +/- 19.2% and 22.2 +/- 16.0%, respectively [p = 0.022]; reversible defect size 18.0 +/- 16.0%, 12.1 +/- 11.6% and 8.2 +/- 7.8%, respectively [p = 0.006]). Occlusion of the infarct-related artery was also more common in patients with DD genotype (odds ratio 3.9, 95% confidence interval 1.4 to 11.0). Multivariate analysis showed that the I/D genotype was an independent predictor of perfusion defect size and patency of the infarct-related artery (p = 0.001). CONCLUSIONS: DD genotype was associated with a larger ischemic defect and occlusion of the infarct-related artery. Patients with DD genotype, having a larger ischemic defect, are expected to be at a greater risk for subsequent cardiovascular events.

Detection of left anterior descending coronary artery stenosis in patients with left bundle branch block: exercise, adenosine or dobutamine imaging?

OBJECTIVES: This study sought to assess the diagnostic value of myocardial perfusion imaging during exercise and pharmacologic stress in patients with left bundle branch block. BACKGROUND: Patients with left bundle branch block often have septal perfusion defects during exercise perfusion tomography that mimic defects caused by coronary artery disease. These defects appear to be less frequent during pharmacologic stress using adenosine or dipyridamole. Data are scantly on the value of dobutamine tomography in these patients. METHODS: We studied 383 consecutive patients with left bundle branch block referred for perfusion scintigraphy over a 5-year span. Perfusion tomography was performed in conjunction with exercise in 206 patients, adenosine in 127 and dobutamine in 50. Coronary angiography was performed within 1 month of the nuclear study in 77, 50 and 27 patients, respectively. RESULTS: Exercise, adenosine and dobutamine tomography had similar sensitivity and specificity for the detection of > 50% stenosis in the left circumflex (74% and 96%; 50% and 100%; 63% and 91%, respectively) and right coronary arteries (96% and 86%; 82% and 91%; 79% and 100%, respectively) and similar sensitivity for left anterior descending coronary artery stenosis (88%, 79% and 100%, respectively). However, the false-positive rate for septal defects was higher by exercise tomography (26 [46%] of 57) than by pharmacologic methods (5 [10%] of 48, p < 0.001), and there was no significant difference between adenosine (4 [11%] of 35) and dobutamine (1 [8%] of 13, p = 0.7). The specificity and predictive value of a positive test response for left anterior descending coronary artery stenosis were 36% and 51% for exercise compared with 81% and 85% for adenosine (p < or = 0.001) and 80% and 90% for dobutamine (p < 0.05), respectively. CONCLUSIONS: In patients with left bundle branch block, pharmacologic stress is more specific than exercise tomography in the diagnosis of left anterior descending coronary artery stenosis. Dobutamine and adenosine tomography appear to be equally specific in these patients.

Quantitative exercise thallium-201 single photon emission computed tomography for the enhanced diagnosis of ischemic heart disease.

The clinical utility of exercise thallium-201 single photon emission computed tomography was investigated in 360 consecutive patients who had concomitant coronary arteriography. Tomographic images were assessed visually and from computer-quantified polar maps. Sensitivity for detecting coronary artery disease was comparably high using quantitative and visual analysis, although specificity tended to improve using the former method (87% versus 76%, p = 0.09). Quantitative analysis was superior to the visual method for identifying left anterior descending (81% versus 68%, p less than 0.05) and circumflex coronary artery (77% versus 60%, p less than 0.05) stenoses and detected most patients (92%) with multivessel coronary artery disease. Multivessel involvement was correctly predicted in 65% of the patients with more than one critically stenosed vessel. Exercise variables in patients with significant coronary artery disease were similar whether the tomographic images were normal or abnormal. However, patients with coronary stenoses and normal versus abnormal tomograms had a trend toward more single vessel disease (79% versus 62%, p = 0.07) and moderate coronary stenosis (66% versus 28%, p less than 0.001), but had less proximal left anterior descending artery involvement (8% versus 34%, p = 0.05). Computer-quantified perfusion defect size was directly related to the extent of coronary artery disease. Intra- and interobserver agreement for quantifying defects were excellent (r = 0.98 and 0.97, respectively). In conclusion, quantitative thallium-201 tomography offers improved detection of coronary artery disease, localization of the anatomic site of coronary stenosis, prediction of multivessel involvement and accurate determination of perfusion defect size, while maintaining a high specificity. Quantification of perfusion defects with single photon tomography may become important for assessing the effects of coronary reperfusion and prognostically stratifying patients with coronary artery disease.

Simultaneous assessment of myocardial perfusion and left ventricular function during transient coronary occlusion.

OBJECTIVES: We used technetium-99m sestamibi imaging to evaluate the magnitude of changes in left ventricular function and perfusion and to investigate their interdependence during transient coronary occlusion. BACKGROUND: Transient coronary occlusion during coronary angioplasty provides a unique opportunity for examining the effects of acute myocardial ischemia on left ventricular function and perfusion. METHODS: Thirty-five patients with normal left ventricular function underwent first-pass radionuclide angiography with technetium-99m sestamibi using a multicrystal gamma camera during balloon occlusion of a coronary artery. Single-photon tomography was performed 2.1 +/- 1.7 h later. Subsequently, all scans were repeated at rest. RESULTS: The mean size +/- SD of the perfusion defect during coronary occlusion was 23 +/- 18%, with significantly larger defects observed for occlusions of the left anterior descending coronary artery (39 +/- 20%) than for occlusions of the left circumflex (15 +/- 11%) or right (15 +/- 9%) coronary artery (p < 0.05). The mean change in ejection fraction from recovery to occlusion was -17 +/- 17% and was significantly larger for left anterior descending (-26 +/- 21%) and left circumflex (-15 +/- 11%) than for right (-8 +/- 10%) coronary artery occlusions (p < 0.05). For the entire group, ejection fraction during occlusion correlated significantly with perfusion defect size (r = 0.63, p = 0.0004), whereas the extent of ischemic myocardium correlated with the decrease in ejection fraction (r = 0.69, p = 0.0001). The defects present during occlusion reversed within a few hours. CONCLUSIONS: Changes in left ventricular function and perfusion develop pari passu during coronary occlusion and are more severe when the left anterior descending artery is occluded. Although a significant correlation exists between the extent of the perfusion defect and the severity of the decrease in ejection fraction, there is a substantial individual variation with respect to changes in both myocardial perfusion and ventricular function during acute coronary occlusion.

Transdermal nitroglycerin patch therapy reduces the extent of exercise-induced myocardial ischemia: results of a double-blind, placebo-controlled trial using quantitative thallium-201 tomography.

OBJECTIVES: This study prospectively evaluated whether transdermal nitroglycerin patches could limit the extent of exercise-induced left ventricular ischemia as assessed by quantitative thallium-201 tomography. BACKGROUND: Although antianginal medications are effective at reducing chest pain symptoms in patients with coronary artery disease, there is limited evidence that these agents can also reduce myocardial ischemia. METHODS: This was a randomized, double-blind, parallel, placebo-controlled trial evaluating nitroglycerin patch therapy in patients in stable condition with angiographic coronary artery disease and no previous myocardial infarction. All patients were weaned from antianginal agents and had a baseline symptom-limited treadmill test followed by thallium-201 tomography. Forty patients with perfusion defects involving > or = 5% of the left ventricle were randomized to receive either intermittent (12 h on/off) active nitroglycerin patch therapy (0.4 mg/h) or placebo. Exercise tomography was repeated a mean (+/- SD) of 6.1 +/- 1.8 days after randomization. RESULTS: Patients randomized to receive active patch therapy had a significant reduction in their total perfusion defect size (-8.9 +/- 11.1%) compared with placebo-treated patients (-1.8 +/- 6.1%, p = 0.04), which was most apparent in those with the largest (> or = 20%) baseline perfusion defects (-11.4 +/- 13.4% vs. 1.0 +/- 3.6%, respectively, p < 0.02). Furthermore, 7 (33%) of 21 patients receiving active therapy had a > or = 10% decrease in their perfusion defects compared with only 1 (5%) of 19 patients randomized to receive placebo (p = 0.002). Nitrate therapy did not significantly reduce heart rate, blood pressure or double product, indicating benefit through enhancement of coronary blood flow. CONCLUSIONS: Short-term, intermittent nitroglycerin patch therapy significantly reduces myocardial ischemia, particularly in patients with large ischemic perfusion defects. Thallium-201 tomography can be used to assess sequential changes in the extent of exercise-induced left ventricular ischemia.

Serial quantitative planar technetium-99m isonitrile imaging in acute myocardial infarction: efficacy for noninvasive assessment of thrombolytic therapy.

Technetium-99m isonitrile is a new myocardial perfusion imaging agent that accumulates according to the distribution of myocardial blood flow. However, unlike thallium-201, it does not redistribute over time. This imaging agent was used with serial quantitative planar imaging to assess the initial risk area of infarction, its change over time and the relation to infarct-related artery patency in 30 patients with a first acute myocardial infarction. Twenty-three of 30 patients were treated with recombinant tissue-type plasminogen activator (rt-PA) within 4 h after the onset of chest pain. Seven patients were treated in the conventional manner without thrombolytic therapy. Technetium-99m isonitrile was injected before or at the initiation of thrombolytic therapy, and imaging was performed several hours later. These initial images demonstrated the area at risk. Repeat imaging was performed 18 to 48 h later and at 6 to 14 days after the onset of myocardial infarction to visualize the ultimate extent of infarction. The initial area at risk varied greatly (range defect integral 2 to 61) both in patients treated with rt-PA and in those who received conventional treatment. For the total group, the initial imaging defect decreased in size in 20 patients and was unchanged or larger in 10 patients. Patients with a patent infarct-related artery had a significantly greater decrease in defect size than did patients with persistent coronary occlusion (-51 +/- 38% versus -1 +/- 26%, p = 0.0001). All patients with a decrease in defect size greater than 30% had a patent infarct-related artery. In 12 patients who also had predischarge quantitative exercise thallium-201 imaging, good agreement existed between the extent and severity of myocardial perfusion defect on the last technetium-99m isonitrile study before discharge and that noted on delayed thallium-201 imaging. It is concluded that serial planar technetium-99m isonitrile myocardial imaging in patients with acute myocardial infarction undergoing thrombolytic therapy offers a new quantitative noninvasive approach for assessment of the initial risk zone as well as the success of reperfusion.

Relation of perfusion defects observed with myocardial contrast echocardiography to the severity of coronary stenosis: correlation with thallium-201 single-photon emission tomography.

It has been previously shown that myocardial contrast echocardiography is a valuable technique for delineating regions of myocardial underperfusion secondary to coronary occlusion and to critical coronary stenoses in the presence of hyperemic stimulation. The aim of this study was to determine whether myocardial contrast echocardiography performed with a stable solution of sonicated albumin could detect regions of myocardial underperfusion resulting from various degrees of coronary stenosis. The perfusion defect produced in 16 open chest dogs was compared with the anatomic area at risk measured by the postmortem dual-perfusion technique and with thallium-201 single-photon emission tomography (SPECT). During a transient (20-s) coronary occlusion, a perfusion defect was observed with contrast echocardiography in 14 of the 15 dogs in which the occlusion was produced. The perfusion defect correlated significantly with the anatomic area at risk (r = 0.74; p less than 0.002). During dipyridamole-induced hyperemia, 12 of the 16 dogs with a partial coronary stenosis had a visible area of hypoperfusion by contrast echocardiography. The four dogs without a perfusion defect had a stenosis that resulted in a mild (0% to 50%) reduction in dipyridamole-induced hyperemia. The size of the perfusion defect during stenosis correlated significantly with the anatomic area at risk (r = 0.61; p = 0.02). Thallium-201 SPECT demonstrated a perfusion defect in all 14 dogs analyzed during dipyridamole-induced hyperemia; the size of the perfusion defect correlated with the anatomic area at risk (r = 0.58; p less than 0.03) and with the perfusion defect by contrast echocardiography (r = 0.58; p less than 0.03). Thus, myocardial contrast echocardiography can be used to visualize and quantitate the amount of jeopardized myocardium during moderate to severe degrees of coronary stenosis. The results obtained show a correlation with the anatomic area at risk similar to that obtained with thallium-201 SPECT.

Quantification of left ventricular performance during transient coronary occlusion at various anatomic sites in humans: a study using tantalum-178 and a multiwire gamma camera.

To study the functional significance of transient coronary occlusion on systolic and diastolic left ventricular function relative to the anatomic site of occlusion, first-pass radionuclide angiography with a mobile multiwire gamma camera using tantalum-178 (dose activity less than or equal to 84 mCi/elution) was performed in 46 patients undergoing balloon coronary angioplasty. First-pass images were acquired immediately before angioplasty and during the last 30 s of a 60-s balloon inflation in 23 left anterior descending arteries, 18 right coronary arteries, 8 circumflex arteries and 3 diagonal coronary arteries. Occlusion of the left anterior descending artery resulted in significant decreases in left ventricular ejection fraction (54.6 +/- 12.7% to 32.3 +/- 10.6%, p = 0.0001) and peak filling rate (2.48 +/- 0.68 to 1.75 +/- 0.64 end-diastolic volumes/s, p = 0.0001), accompanied by severe abnormalities in regional function and left ventricular dilation. Right coronary artery occlusion caused inferior hypokinesia, but did not significantly change left ventricular ejection fraction (48.5 +/- 12.4% vs. 45.8 +/- 12.5%, p = NS) or peak filling rate (2.05 +/- 0.81 vs. 2.09 +/- 0.81 end-diastolic volumes/s, p = NS). Circumflex artery occlusion resulted in mild wall motion deterioration and a borderline decrease in ejection fraction (54.7 +/- 11.4% to 50.5 +/- 12%, p = 0.057). Diagonal artery occlusion did not cause significant changes in left ventricular ejection fraction or filling rate. The decrease in left ventricular ejection fraction during coronary occlusion was 9 +/- 25% and 27 +/- 22%, respectively, in those arteries with and without collateral supply (p = 0.052). These data provide strong evidence for the critical importance of the left anterior descending artery and the secondary role of the other coronary arteries in maintaining global systolic and diastolic left ventricular function and suggest a protective role of collateral vessels during coronary occlusion.